Risk for incident comorbidities, non-hepatic cancer and mortality in acute hepatic porphyria: A matched cohort study in 1,244 individuals.

The acute hepatic porphyrias (AHP) are associated with long-term complications such as primary liver cancer, hypertension and chronic kidney disease. Data on other related comorbidities are scarce. In this register-based, matched cohort study, we assessed the risks of non-hepatic cancers, cardiovascular diseases, renal diseases, psychiatric disorders, and mortality in relation to porphyria type, sex and biochemical disease activity. All patients in the Swedish porphyria register with a verified AHP diagnosis during 1987-2015 were included. The biochemical activity of acute intermittent porphyria was assessed using recorded maximal urinary porphobilinogen (U-PBG). Data on incident comorbidities and mortality were collected from national health registries. Cumulative incidences, rates and hazards were compared to reference individuals from the general population, matched 1:10 by age, sex and county. We identified 1,244 patients with AHP with a median follow-up of 19 years. Health registries identified 149 AHP-subjects (12.0%) with non-hepatic cancer, similar to 1,601 (13.0%) in the matched reference population (n=12,362). Patients with AHP had a higher risk of kidney cancer (0.8% vs. 0.2%, p<0.001), hypertension, and chronic kidney disease but no increase in risk for cardiovascular disease, except for cerebrovascular disease in patients with elevated U-PBG, (aHR=1.40[95%CI:1.06-1.85]). Mortality risk during follow-up was higher among patients with AHP (21% vs. 18%, p=0.001), and associated with primary liver cancer, female sex and biochemical activity. In conclusion: AHP is associated with an increased risk of kidney cancer, hypertension, chronic kidney disease and mortality but not with cardiovascular disease or other non-hepatic cancers. This article is protected by copyright. All rights reserved.